Occupational exposure to crystalline silica can be associated with either chronic or acute pulmonary disease. Chronic silicosis becomes manifest 20 to 40 years after first exposure and is characterized by development of concentric hyalinized nodular lesions in the lung with the development of dyspnea over a period of several decades. Acute silicosis, on the other hand, is manifested by a rapid onset after exposure and is characterized by the accumulation of an amorphous granular lipoprotein exudate in the airspaces and rapid development of respiratory disability within a few years.
Information is growing concerning the etiology of chronic silicosis. Studies suggest that several mechanisms may be involved in the development of fibrosis. Lung injury may result from silica-induced release of lysosomal enzymes from alveolar macrophages (1, 2). In addition, silica-induced activation of superoxide anion and hydrogen peroxide release from alveolar macrophages may result in oxidant-induced damage to lung parenchyma (3). Silica exposure can also result in the release of mediators from alveolar macrophages which enhance the proliferation of fibroblasts and the synthesis of collagen by these pneumocytes (4, 5).
In comparison with chronic silicosis, very little is known concerning the development of acute silicosis. Because the pulmonary responses to silica differ in the chronic and acute presentation of disease, it does not seem likely that acute silicosis can be explained simply as the response of the lung to high levels of silica. Acute silicosis is commonly associated with sandblasting, rock drilling, tunnelling, and silica mill operations, i.e., operations in which silica particles are crushed or sheared (6). Therefore, it is possible that freshly sheared silica may have surface properties that make it more reactive with lung tissue than aged silica, and that it is this unique reactivity of freshly sheared silica that leads to manifestation of acute pulmonary disease.
Studies have suggested that freshly fractured silica may exhibit surface reactivity not found in aged silica. Hochstrasser and Antinini (7) reported that silicon-based radicals could be generated upon cleavage of a quartz crystal under ultra-high vacuum (10.sup.-10 mm Hg). Karmanova and colleagues (8) reported release of singlet oxygen from silica dust upon heating, whereas Kolbanev and associates (9) reported generation of H.sub.2 O.sub.2 from the reaction of freshly ground silica with water. In addition, Marasas and Harington (10) reported that silica exhibits oxidant properties that may be related to its pathogenicity.
Vallyathan et al (Am. Rev. Respir. Dis., 138:1213-1219 (1988)) have reported that freshly fractured silica exhibits surface characteristics and biological reactivity distinct from aged silica, that grinding of silica produced .about.18.sup.18 Si and Si--O (silicon based radicals per gram of dust) on the particulate surface, which were characterized by an electron spin resonance (ESR) spectrum centered around g=2.0015, and that these radicals react with aqueous media to produce OH radicals (demonstrated using a DMPO spin trap); that when compared to aged silica, freshly ground silica exhibits a greater cytotoxic effect on cellular membrane integrity (i.e., it showed a 1.5-fold increase in lactate dehydrogenase (LDH) release from macrophages, a 36-fold increase in hemolytic activity, and a 3-fold increase in the ability to induce lipid peroxidation as compared with aged silica).
It was postulated by Vallyathan et al in the same report that because acute silicosis is frequently associated with occupations in which freshly fractured crystalline silica of respirable size is generated, and that fracture-generated silicon-based radicals may play a significant role in the pathogenesis of the disease. Am. Rev. Respir. Dis., 138:1213-1219 (1988) is herein incorporated by reference.